Impact of Baseline HIV-1 Tropism on Viral Response and CD4 Cell Count Gains in HIV-Infected Patients Receiving First-line Antiretroviral Therapy

Human immunodeficiency virus type 1 (HIV-1) tropism for the chemokine receptors CCR5 and CXCR4 has been shown to be associated to disease progression [1–3]. Viruses that exclusively use the CCR5 receptor to enter the target cells (R5 viruses) are generally predominant at early stages of HIV-1 infection, whereas the emergence of CXCR4-using viruses (X4 viruses) generally occurs at later stages [4–6]. The presence of X4 viruses is consistently associated with low CD4+ T-cell counts and accelerated disease progression, although it is still unclear whether it is cause or consequence of disease progression [6, 7]. In the absence of antiretroviral therapy, X4 viruses are associated with faster CD4 cell count decreases regardless of baseline CD4 cell count or viral load [3, 4]. However, in the presence of antiretroviral therapy, results are controversial. Although some authors have reported that patients harboring X4 viruses display poorer immunological recovery despite comparable viral load suppression than those patients exclusively infected with R5 viruses [8, 9], other authors have reported that CD4 cell count increases and virologic response rates to antiretroviral therapy occur regardless viral tropism [4]. Disagreements might be due to the heterogeneity of study populations, mainly as result of differences in baseline CD4 cell count, viral load, antiretrovirals used, and/or time of follow-up after beginning therapy. In this regard, a prospective clinical trial comparing antiretroviral regimens could be an excellent opportunity to assess retrospectively the impact of HIV-1 tropism on treatment outcomes.